Boronic acid monomers and methods of making boronic acid monomers

ABSTRACT

Boronic acid monomers, methods of making boronic acid monomer, and the like, are provided. Embodiments of the present disclosure are advantageous in that the boronic acid monomers are water soluble at a neutral pH, which is uncommon for boronic acids. As a result, the boronic acid monomers can be used in aqueous polymerization reactions with other hydrophilic monomers to yield polymers including boronic acids and esters.

CLAIM OF PRIORITY TO RELATED APPLICATION

This application claims priority to co-pending U.S. provisionalapplication entitled “BORONIC ACID MONOMERS AND METHODS OF MAKINGBORONIC ACID MONOMERS” having Ser. No. 62/723,569 filed on Aug. 28,2018, which is entirely incorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

This invention was made with government support under DMR1410223 awardedby the National Science Foundation. The government has certain rights inthe invention.

BACKGROUND

Compounds including boronic acid have been found to be useful in manyareas based on their unique and versatile reactivity as well as theirstability. Some areas in which compounds including boronic acid havebeen found useful include acid catalysis, metal-catalysis, molecularsensing, and biomedical applications, to name but a few.

SUMMARY

Embodiments of the present disclosure provide for boronic acid monomers,methods of making a boronic acid monomer, and the like. In anembodiment, the present disclosure provides for a compositioncomprising: a monomer selected from one of the following:

wherein Y is O, NH, or N(alkyl) and wherein Z is a polymerizable group.The polymerizable group can be selected from: an acrylamide group, amethacrylamide group, an acrylate group, a methacrylate group, astyrenic group, N-carboxyanhydride group, a N-thiocarboxyanhydridegroup, an alkenyl group, a norbornene group, or an oxynorbornene group.

In an embodiment, the present disclosure provides for a method of makinga monomer, comprising:

wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl), andwherein Z is a polymerizable group.

In an embodiment, the present disclosure provides for a method of makinga monomer, comprising:

wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl), andwherein Z is a polymerizable group.

In an embodiment, the present disclosure provides for a monomer,comprising:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl),wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl), andn is 1 to 4.

In an embodiment, the present disclosure provides for a method of makinga monomer, comprising:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl),wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl), andn is 1 to 4.

DETAILED DESCRIPTION

This disclosure is not limited to particular embodiments described, andas such may, of course, vary. The terminology used herein serves thepurpose of describing particular embodiments only, and is not intendedto be limiting, since the scope of the present disclosure will belimited only by the appended claims.

Where a range of values is provided, each intervening value, to thetenth of the unit of the lower limit unless the context clearly dictatesotherwise, between the upper and lower limit of that range and any otherstated or intervening value in that stated range, is encompassed withinthe disclosure. The upper and lower limits of these smaller ranges mayindependently be included in the smaller ranges and are also encompassedwithin the disclosure, subject to any specifically excluded limit in thestated range. Where the stated range includes one or both of the limits,ranges excluding either or both of those included limits are alsoincluded in the disclosure.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentdisclosure. Any recited method may be carried out in the order of eventsrecited or in any other order that is logically possible.

Embodiments of the present disclosure will employ, unless otherwiseindicated, techniques of electrochemistry, analytical chemistry, polymerchemistry, material science, and the like, which are within the skill ofthe art. Such techniques are explained fully in the literature.

Prior to describing the various embodiments, the following definitionsare provided and should be used unless otherwise indicated.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art of microbiology, molecular biology, medicinal chemistry, and/ororganic chemistry. Although methods and materials similar or equivalentto those described herein can be used in the practice or testing of thepresent disclosure, suitable methods and materials are described herein.

As used in the specification and the appended claims, the singular forms“a,” “an,” and “the” may include plural referents unless the contextclearly dictates otherwise. Thus, for example, reference to “a support”includes a plurality of supports. In this specification and in theclaims that follow, reference will be made to a number of terms thatshall be defined to have the following meanings unless a contraryintention is apparent.

Definitions:

The term “substituted” refers to any one or more hydrogens on thedesignated atom that can be replaced with a selection from the indicatedgroup, provided that the designated atom's normal valence is notexceeded, and that the substitution results in a stable compound.

The term “aliphatic group” refers to a saturated or unsaturated, linearor branched, substituted or unsubstituted hydrocarbon group andencompasses alkyl, alkenyl, and alkynyl groups, for example.

As used herein, “alkyl” or “alkyl group” refers to a saturated aliphatichydrocarbon radical which can be straight or branched and/or substitutedor unsubstituted, having 1 to 20 carbon atoms, wherein the stated rangeof carbon atoms includes each intervening integer individually, as wellas sub-ranges (e.g., C1 to C6, C1 to C4, and the like). Examples ofalkyl include, but are not limited to methyl, ethyl, n-propyl,iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, and sec-pentyl,and the like.

As used herein, “alkenyl” or “alkenyl group” refers to an aliphatichydrocarbon radical which can be straight or branched and/or substitutedor unsubstituted, containing at least one carbon-carbon double bond,having 2 to 20 carbon atoms, wherein the stated range of carbon atomsincludes each intervening integer individually, as well as sub-ranges(e.g., C1 to C6, C1 to C4, and the like). Examples of alkenyl groupsinclude, but are not limited to, ethenyl, propenyl, n-butenyl,iso-butenyl, 3-methylbut-2-enyl, n-pentenyl, heptenyl, octenyl, decenyl,and the like.

The term “substituted,” as in “substituted alkyl” and the like meansthat the substituted group may contain in place of one or more hydrogensa group such as halogen or hydroxy. In an embodiment, “substituted”includes the substituted group may contain in place of one or morehydrogens a group such as halogen or an alkyl group (e.g., a linear orbranched C1 to C4 moiety).

As used herein, “halo”, “halogen”, or “halogen radical” refers to afluorine, chlorine, bromine, and iodine, and radicals thereof. Further,when used in compound words, such as “haloalkyl” or “haloalkenyl”,“halo” refers to an alkyl or alkenyl radical in which one or morehydrogens are substituted by halogen radicals. Examples of haloalkylinclude, but are not limited to, trifluoromethyl, trichloromethyl,pentafluoroethyl, and pentachloroethyl.

Discussion:

Embodiments of the present disclosure provide for boronic acid monomers,methods of making a boronic acid monomer, and the like. Embodiments ofthe present disclosure are advantageous in that the boronic acidmonomers are water soluble at a neutral pH (e.g., a physiological pH ofabout 7.4), which is uncommon for boronic acids. As a result, theboronic acid monomers can be used in aqueous polymerization reactionswith other hydrophilic monomers to yield polymers including boronicacids and esters, which can be used in numerous applications such asphysiological applications (e.g., enzymatic inhibitor, drug delivery,and so on), sensing (e.g., for saccharides), protein conjugation (e.g.,for immobilization to glycoproteins), hydrogels, and the like.

In an aspect, the boronic acid monomer can have one of the followingstructures:

In an aspect, Y can be O, NH, or N(alkyl). In aspects, the alkyl group(e.g., independently for R and N(alkyl) (X and/or Y) can be a C1 to C6alkyl group, a C1 to C3 alkyl group, or a C1 alkyl group. In anembodiment, Z can be a polymerizable group. The polymerizable group canbe: an acrylamide group, a methacrylamide group, an acrylate group, amethacrylate group, a styrenic group, N-carboxyanhydride group, aN-thiocarboxyanhydride group, an alkenyl group, a norbornene group, oran oxynorbornene group. Each of the boronic acid monomers describedabove and herein are water soluble at a neutral pH (e.g., about 7.2 to7.6) and in particular, at a physiological pH of about 7.4. This isadvantageous in aqueous polymerization reactions with other hydrophilicmonomers.

In an embodiment, the boronic acid monomer can have one of the followingstructures:

These compounds can be water soluble at a neutral pH of about 7.2 to 7.6or about 7.4. In an aspect, R can be H or an alkyl group. In anembodiment, X can be O, NH, or N(alkyl). In an embodiment, Y can be O,NH, or N(alkyl). In an embodiment, Z can be OH, NH₂, or a polymerizablegroup, while n is 0 to 4 or 1 to 4. In aspects, the alkyl group (e.g.,independently for R and N(alkyl) (X and/or Y) can be a C1 to C6 alkylgroup, a C1 to C3 alkyl group, or a C1 alkyl group. In an aspect, R canbe H or a methyl group. In an embodiment, the polymerizable group canbe: a styrenic group, N-carboxyanhydride group, a N-thiocarboxyanhydridegroup, an alkenyl group, a norbornene group, or an oxanorbornene group.

In aspects, the boronic acid monomer can be made using the followingreaction scheme:

In an embodiment, Y can be O, NH, or N(alkyl). In an embodiment, Q canbe OH, NH₂, or NH(alkyl). In an aspect, the alkyl group for Y and/or Qcan independently be can be a C1 to C6 alkyl group, a C1 to C3 alkylgroup, or a C1 alkyl group. In an embodiment, Z can be a polymerizablegroup. In an embodiment, the polymerizable group can be: an acrylamidegroup, a methacrylamide group, an acrylate group, a methacrylate group,a styrenic group, N-carboxyanhydride group, a N-thiocarboxyanhydridegroup, an alkenyl group, a norbornene group, or an oxanorbornene group,while the polymerizable compound is the compound from which thepolymerizable group is derived (e.g., via removal of a H). Inparticular, the polymerizable compound can be a styrenic compound,N-carboxyanhydride compound, a N-thiocarboxyanhydride compound, analkenyl compound, a norbornene compound, or an oxynorbornene compound.In an embodiment, the polymerization can be initiated usingphoto-initiation, thermal initiators (e.g., azo compounds, peroxides,and the like), redox initiators (e.g., ammonium persulfate withtetramethylethylenediamine, and the like), suitable nucleophiles (e.g.,butyl lithium, alkoxides, or other anionic initiators), or metathesiscatalysts (e.g., catalyst based on transition metals such as W, Mo, Re,Ru, and Ti). In an embodiment, the pH can be about 4 to 11 and thetemperature can be about 0 to about 110° C. for the polymerization.

In a particular embodiment, the boronic acid monomer can be made usingthe following reaction scheme:

In an embodiment, R can be H or an alkyl group. In an embodiment, X canbe O, NH, or N(alkyl). In an embodiment, Y can be O, NH, or N(alkyl). Inan embodiment, Q can be OH, NH₂, or NH(alkyl), while n is 0 to 4 or 1 to4. In an aspect, the alkyl group for R, X, Y and/or Q can independentlybe can be a C1 to C6 alkyl group, a C1 to C3 alkyl group, or a C1 alkylgroup. In an embodiment, R can be H or a methyl group. In an embodiment,the polymerization can be initiated using photo-initiation, thermalinitiators, or redox initiators. In an embodiment, the pH can be about 4to 11 and the temperature can be about 0 to about 100° C. for thepolymerization.

In an embodiment, the boronic acid monomer can be made using thefollowing reaction scheme:

In an embodiment, Q can be OH, NH₂, or NH(alkyl). In an aspect, thealkyl group for Q can independently be can be a C1 to C6 alkyl group, aC1 to C3 alkyl group, or a C1 alkyl group. In an embodiment, Z can be apolymerizable group. In an embodiment, the polymerizable group can be:an acrylamide group, a methacrylamide group, an acrylate group, amethacrylate group, a styrenic group, N-carboxyanhydride group, aN-thiocarboxyanhydride group, an alkenyl group, a norbornene group, oran oxynorbornene group, while the polymerizable compound is the compoundfrom which the polymerizable group is derived (e.g., via removal of aH). In particular, the polymerizable compound can be a styreniccompound, N-carboxyanhydride compound, a N-thiocarboxyanhydridecompound, an alkenyl compound, a norbornene compound, or anoxynorbornene compound. In an embodiment, the polymerization can beinitiated using photo-initiation, thermal initiators, or redoxinitiators. In an embodiment, the pH can be about 4 to 11 and thetemperature can be about 0 to about 110° C. for the polymerization.

In a particular embodiment, the boronic acid monomer can be made usingthe following reaction scheme:

In an embodiment, R can be H or an alkyl group. In an embodiment, X canbe O, NH, or N(alkyl). In an embodiment, Q can be OH, NH₂, or NH(alkyl),while n is 1 to 4. In an aspect, the alkyl group for R, X, Y and/or Qcan independently be can be a C1 to C6 alkyl group, a C1 to C3 alkylgroup, or a C1 alkyl group. In an embodiment, R can be H or a methylgroup. In an embodiment, the polymerization can be initiated usingphoto-initiation. In an embodiment, the pH can be about 4 to 11 and thetemperature can be about 0 to about 110° C. for the polymerization.

It should be noted that ratios, concentrations, amounts, and othernumerical data may be expressed herein in a range format. It is to beunderstood that such a range format is used for convenience and brevity,and thus, should be interpreted in a flexible manner to include not onlythe numerical values explicitly recited as the limits of the range, butalso to include all the individual numerical values or sub-rangesencompassed within that range as if each numerical value and sub-rangeis explicitly recited. To illustrate, a concentration range of “about0.1% to about 5%” should be interpreted to include not only theexplicitly recited concentration of about 0.1 wt % to about 5 wt %, butalso include individual concentrations (e.g., 1%, 2%, 3%, and 4%) andthe sub-ranges (e.g., 0.5%, 1.1%, 2.2%, 3.3%, and 4.4%) within theindicated range. In an embodiment, the term “about” can includetraditional rounding according to significant figures of the numericalvalue. In addition, the phrase “about ‘x’ to ‘y’” includes “about ‘x’ toabout ‘y’”.

Many variations and modifications may be made to the above-describedembodiments. All such modifications and variations are intended to beincluded herein within the scope of this disclosure and protected by thefollowing claims.

we claim:
 1. A composition comprising: a monomer selected from one ofthe following:

wherein Y is O, NH, or N(alkyl), wherein Z is a polymerizable group. 2.The composition of claim 1, wherein the polymerizable group is selectedfrom: an acrylamide group, a methacrylamide group, an acrylate group, amethacrylate group, a styrenic group, N-carboxyanhydride group, aN-thiocarboxyanhydride group, an alkenyl group, a norbornene group, oran oxynorbornene group.
 3. The composition of claim 1, wherein themonomer selected from one of the following:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl), and nis 0 to
 4. 4. The composition of claim 3, wherein R is H or methylgroup.
 5. The composition of claim 1, wherein the monomer is selectedfrom the following:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl), and nis 0 to
 4. 6. The composition of claim 1, wherein the monomer is:

wherein the polymerizable group is selected from: an acrylamide group, amethacrylamide group, an acrylate group, a methacrylate group, astyrenic group, N-carboxyanhydride group, a N-thiocarboxyanhydridegroup, an alkenyl group, a norbornene group, or an oxynorbornene group.7. The composition of claim 1, wherein the monomer:

wherein the polymerizable group is selected from: an acrylamide group, amethacrylamide group, an acrylate group, a methacrylate group, astyrenic group, N-carboxyanhydride group, a N-thiocarboxyanhydridegroup, an alkenyl group, a norbornene group, or an oxynorbornene group.8. The composition of claim 1, wherein the monomer selected from one ofthe following:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl), and nis 0 to
 4. 9. The composition of claim 1, wherein the monomer selectedfrom one of the following:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl), and nis 0 to
 4. 10. A method of making a monomer, comprising:

wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl),wherein Z is a polymerizable group.
 11. The method of claim 10, whereinthe polymerizable group is selected from: a styrenic group,N-carboxyanhydride group, a N-thiocarboxyanhydride group, an alkenylgroup, a norbornene group, or an oxynorbornene group.
 12. The method ofclaim 10, wherein the polymerizable compound is selected from: astyrenic compound, N-carboxyanhydride compound, a N-thiocarboxyanhydridecompound, an alkenyl compound, a norbornene compound, or anoxynorbornene compound.
 13. A method of making a monomer, comprising:

wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl),wherein Z is a polymerizable group.
 14. The method of claim 13, whereinthe polymerizable group is selected from: a styrenic group,N-carboxyanhydride group, a N-thiocarboxyanhydride group, an alkenylgroup, a norbornene group, or an oxynorbornene group.
 15. The method ofclaim 13, wherein the polymerizable compound is selected from: astyrenic compound, N-carboxyanhydride compound, a N-thiocarboxyanhydridecompound, an alkenyl compound, a norbornene compound, or anoxynorbornene compound.
 16. A method of making a monomer, comprising:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl),wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl), andn is 1 to
 4. 17. The method of claim 16, wherein R is H or methyl group.18. A method of making a monomer, comprising:

wherein R is H or an alkyl group, wherein X is O, NH, or N(alkyl),wherein Y is O, NH, or N(alkyl), wherein Q is OH, NH₂, or NH(alkyl), andn is 1 to
 4. 19. The method of claim 18, wherein R is H or methyl group.